Abstract 6363: The biparatopic antibody KA-3005 against MET is suitable for developing antibody-drug conjugates (ADCs) to treat MET-expressing cancers

Abstract

Abstract MET is overexpressed in a significant fraction of lung (25%-50%) and gastroesophageal cancers, making the targeting of MET with an antibody-drug conjugate (ADC) an attractive approach. Here, we developed a bispecific antibody (BsAb) named KA-3005, targeting two different epitopes within the extracellular domain of MET using our common light chain antibody discovery platform. KA-3005 has a regular antibody structure with an identical light chain, developed using knob-into-hole technology. This antibody exhibits significantly higher avidity to MET expressed on tumor cells, with an EC50 of less than 0.1nM compared to its parent antibodies. It also completely blocks the binding of HGF to MET and the MET downstream pathway at a concentration as low as 1nM. This biparatopic antibody demonstrates a faster internalization rate upon binding to the surface of tumor cells expressing MET than its parent antibodies. KA-3005 effectively suppressed the growth of HCC827-HGF tumors in a xenograft mouse model. Additionally, it has a half-life of more than five days in the blood of Balb/c mice. Finally, we assessed the developability of KA-3005 under different treatments such as high concentration, low pH, repeated freezing and thawing, and high temperature, and it showed neither aggregation nor degradation. In conclusion, this biparatopic antibody, KA-3005, developed with our common light chain antibody discovery platform, is stable and holds potential for the development of ADCs targeting MET. Citation Format: Guojin Wu, Jiabei Liang, Hao Peng, Feng Hao, Tongtong Liu, Jinying Ning. The biparatopic antibody KA-3005 against MET is suitable for developing antibody-drug conjugates (ADCs) to treat MET-expressing cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6363.